rs77214077

Positions:

chrX-154532214-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001360016.2(G6PD):c.1431C>T(p.Pro477=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,209,236 control chromosomes in the GnomAD database, including 161 homozygotes. There are 1,369 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 75 hom., 648 hem., cov: 23)

Exomes 𝑓: 0.0025 ( 86 hom. 721 hem. )

Consequence

G6PD
NM_001360016.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

G6PD (HGNC:4057): (glucose-6-phosphate dehydrogenase) This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

G6PD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-154532214-G-A is Benign according to our data. Variant chrX-154532214-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 93496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
G6PD	NM_001360016.2 linkuse as main transcript	c.1431C>T	p.Pro477=	synonymous_variant	12/13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4 linkuse as main transcript	c.1521C>T	p.Pro507=	synonymous_variant	12/13		NP_000393.4
G6PD	NM_001042351.3 linkuse as main transcript	c.1431C>T	p.Pro477=	synonymous_variant	12/13		NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10 linkuse as main transcript	c.1431C>T	p.Pro477=	synonymous_variant	12/13	1	NM_001360016.2	ENSP00000377192	P4	P11413-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

2485

AN:

111280

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

637

AN XY:

33544

show subpopulations

Gnomad AFR

AF:

0.0783

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00521

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000189

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00676

AC:

1231

AN:

182188

Hom.:

AF XY:

0.00402

AC XY:

270

AN XY:

67082

show subpopulations

Gnomad AFR exome

AF:

0.0875

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00246

AC:

2702

AN:

1097908

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

721

AN XY:

363322

show subpopulations

Gnomad4 AFR exome

AF:

0.0868

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000629

Gnomad4 OTH exome

AF:

0.00506

GnomAD4 genome

AF:

0.0224

AC:

2499

AN:

111328

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

648

AN XY:

33602

show subpopulations

Gnomad4 AFR

AF:

0.0787

Gnomad4 AMR

AF:

0.00521

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000189

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.0263

EpiCase

AF:

0.000109

EpiControl

AF:

0.000416

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 09, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 27, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Anemia, nonspherocytic hemolytic, due to G6PD deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	curation	Dunham Lab, University of Washington	Sep 01, 2024	Reported in >3 hemi- and homozygotes with normal G6PD activity in red blood cells (BS3). Additional interpretation on ClinVar support benign (BP6). -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 10, 2012

- -

G6PD-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

G6PD deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over